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Q1LZ53

- DNM3A_RAT

UniProt

Q1LZ53 - DNM3A_RAT

Protein

DNA (cytosine-5)-methyltransferase 3A

Gene

Dnmt3a

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 71 (01 Oct 2014)
      Sequence version 1 (30 May 2006)
      Previous versions | rss
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    Functioni

    Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Can actively repress transcription through the recruitment of HDAC activity By similarity.By similarity

    Catalytic activityi

    S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.PROSITE-ProRule annotation

    Enzyme regulationi

    Activated by binding to the regulatory factor DNMT3L.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei660 – 6601S-adenosyl-L-methionineBy similarity
    Active sitei706 – 7061PROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri489 – 51931GATA-type; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri530 – 58657PHD-type; atypicalPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: Ensembl
    2. DNA (cytosine-5-)-methyltransferase activity Source: UniProtKB
    3. DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Source: RGD
    4. DNA binding Source: UniProtKB
    5. metal ion binding Source: UniProtKB-KW
    6. unmethylated CpG binding Source: RGD

    GO - Biological processi

    1. C-5 methylation of cytosine Source: GOC
    2. cellular response to amino acid stimulus Source: Ensembl
    3. DNA methylation Source: UniProtKB
    4. DNA methylation involved in embryo development Source: Ensembl
    5. DNA methylation involved in gamete generation Source: Ensembl
    6. DNA methylation on cytosine within a CG sequence Source: RGD
    7. hypermethylation of CpG island Source: Ensembl
    8. methylation-dependent chromatin silencing Source: Ensembl
    9. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    10. regulation of gene expression by genetic imprinting Source: Ensembl
    11. S-adenosylhomocysteine metabolic process Source: RGD
    12. S-adenosylmethioninamine metabolic process Source: RGD
    13. spermatogenesis Source: Ensembl
    14. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Chromatin regulator, Methyltransferase, Repressor, Transferase

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, S-adenosyl-L-methionine, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_212012. PRC2 methylates histones and DNA.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA (cytosine-5)-methyltransferase 3A (EC:2.1.1.37)
    Short name:
    Dnmt3a
    Gene namesi
    Name:Dnmt3a
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 6

    Organism-specific databases

    RGDi1303336. Dnmt3a.

    Subcellular locationi

    Nucleus By similarity. Cytoplasm By similarity

    GO - Cellular componenti

    1. chromosome, centromeric region Source: Ensembl
    2. cytoplasm Source: UniProtKB
    3. euchromatin Source: UniProtKB
    4. nuclear heterochromatin Source: Ensembl
    5. nuclear matrix Source: UniProtKB
    6. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 908908DNA (cytosine-5)-methyltransferase 3APRO_0000313030Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei102 – 1021PhosphoserineBy similarity
    Modified residuei239 – 2391PhosphoserineBy similarity
    Modified residuei251 – 2511PhosphoserineBy similarity
    Modified residuei257 – 2571PhosphothreonineBy similarity

    Post-translational modificationi

    Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ1LZ53.

    PTM databases

    PhosphoSiteiQ1LZ53.

    Expressioni

    Gene expression databases

    GenevestigatoriQ1LZ53.

    Interactioni

    Subunit structurei

    Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) By similarity. Interacts with DNMT1 and DNMT3B. Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain By similarity. Interacts with the PRC2/EED-EZH2 complex By similarity. Interacts with UBC9, PIAS1 and PIAS2 By similarity. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). Interacts with UHRF1 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ1LZ53.
    SMRiQ1LZ53. Positions 279-420, 623-908.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini257 – 31559PWWPPROSITE-ProRule annotationAdd
    BLAST
    Domaini478 – 610133ADDPROSITE-ProRule annotationAdd
    BLAST
    Domaini630 – 908279SAM-dependent MTase C5-typePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni195 – 399205Interaction with DNMT1 and DNMT3BBy similarityAdd
    BLAST
    Regioni490 – 58293Interaction with the PRC2/EED-EZH2 complexBy similarityAdd
    BLAST
    Regioni637 – 6415S-adenosyl-L-methionine bindingBy similarity
    Regioni682 – 6843S-adenosyl-L-methionine bindingBy similarity
    Regioni887 – 8893S-adenosyl-L-methionine bindingBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi479 – 52749Cys-richAdd
    BLAST

    Domaini

    The PWWP domain is essential for targeting to pericentric heterochromatin.

    Sequence similaritiesi

    Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.PROSITE-ProRule annotation
    Contains 1 ADD domain.PROSITE-ProRule annotation
    Contains 1 GATA-type zinc finger.PROSITE-ProRule annotation
    Contains 1 PHD-type zinc finger.PROSITE-ProRule annotation
    Contains 1 PWWP domain.PROSITE-ProRule annotation
    Contains 1 SAM-dependent MTase C5-type domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri489 – 51931GATA-type; atypicalPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri530 – 58657PHD-type; atypicalPROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG70699.
    GeneTreeiENSGT00390000008341.
    HOGENOMiHOG000230875.
    HOVERGENiHBG051381.
    InParanoidiQ1LZ53.
    KOiK17398.
    OMAiFVGGMCQ.
    OrthoDBiEOG7MWGW6.
    PhylomeDBiQ1LZ53.
    TreeFamiTF329039.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR025766. ADD.
    IPR018117. C5_DNA_meth_AS.
    IPR001525. C5_MeTfrase.
    IPR025811. C5_MeTrfase_3.
    IPR000313. PWWP_dom.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view]
    PfamiPF00145. DNA_methylase. 1 hit.
    PF00855. PWWP. 1 hit.
    [Graphical view]
    SMARTiSM00293. PWWP. 1 hit.
    [Graphical view]
    SUPFAMiSSF53335. SSF53335. 1 hit.
    PROSITEiPS51533. ADD. 1 hit.
    PS00094. C5_MTASE_1. 1 hit.
    PS50812. PWWP. 1 hit.
    PS51679. SAM_MT_C5. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative promoter usage. Align

    Isoform 1 (identifier: Q1LZ53-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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    MPSSGPGDTS ISSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR    50
    KRKHPPVESS DTPKDPAVTT KSQPTAQDSG PSDLLPNGDL EKRSEPQPEE 100
    GSPAAGQKGG APAEGEGTET PPEASRAVEN GCCVTKEGRG ASAGEGKEQK 150
    QTNIESMKME GSRGRLRGGL GWESSLRQRP MPRLTFQAGD PYYISKRKRD 200
    EWLARWKREA EKKAKVIAVM NAVEESQASG ESQKVEEASP PAVQQPTDPA 250
    SPTVATTPEP VGADAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS 300
    WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF 350
    HQATYNKQPM YRKAIYEVLQ VASSRAGKLF PACHDSDESD TGKAVEVQNK 400
    QMIEWALGGF QPSGPKGLEP PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA 450
    KKPRKSTTEK PKVKEIIDER TRERLVYEVR QKCRNIEDIC ISCGSLNVTL 500
    EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR EVLMCGNNNC 550
    CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR 600
    LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG 650
    IQVDRYIASE VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV 700
    IGGSPCNDLS IVNPARKGLY EGTGRLFFEF YRLLHDARPK EGDDRPFFWL 750
    FENVVAMGVS DKRDISRFLE SNPVMIDAKE VSAAHRARYF WGNLPGMNRP 800
    LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK DQHFPVFMNE 850
    KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP 900
    LKEYFACV 908
    Length:908
    Mass (Da):101,669
    Last modified:May 30, 2006 - v1
    Checksum:i6CCE9EB4E9CEB409
    GO
    Isoform 2 (identifier: Q1LZ53-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-219: Missing.

    Show »
    Length:689
    Mass (Da):77,825
    Checksum:i1C75674CFC1C97BE
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 219219Missing in isoform 2. 1 PublicationVSP_029986Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BN000395 mRNA. Translation: CAE52317.1.
    BN000396 mRNA. Translation: CAE52318.1.
    RefSeqiNP_001003957.1. NM_001003957.1. [Q1LZ53-2]
    NP_001003958.1. NM_001003958.1. [Q1LZ53-1]
    UniGeneiRn.92659.

    Genome annotation databases

    EnsembliENSRNOT00000047210; ENSRNOP00000046524; ENSRNOG00000026649. [Q1LZ53-1]
    GeneIDi444984.
    KEGGirno:444984.

    Keywords - Coding sequence diversityi

    Alternative promoter usage

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BN000395 mRNA. Translation: CAE52317.1 .
    BN000396 mRNA. Translation: CAE52318.1 .
    RefSeqi NP_001003957.1. NM_001003957.1. [Q1LZ53-2 ]
    NP_001003958.1. NM_001003958.1. [Q1LZ53-1 ]
    UniGenei Rn.92659.

    3D structure databases

    ProteinModelPortali Q1LZ53.
    SMRi Q1LZ53. Positions 279-420, 623-908.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q1LZ53.

    Proteomic databases

    PaxDbi Q1LZ53.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000047210 ; ENSRNOP00000046524 ; ENSRNOG00000026649 . [Q1LZ53-1 ]
    GeneIDi 444984.
    KEGGi rno:444984.

    Organism-specific databases

    CTDi 1788.
    RGDi 1303336. Dnmt3a.

    Phylogenomic databases

    eggNOGi NOG70699.
    GeneTreei ENSGT00390000008341.
    HOGENOMi HOG000230875.
    HOVERGENi HBG051381.
    InParanoidi Q1LZ53.
    KOi K17398.
    OMAi FVGGMCQ.
    OrthoDBi EOG7MWGW6.
    PhylomeDBi Q1LZ53.
    TreeFami TF329039.

    Enzyme and pathway databases

    Reactomei REACT_212012. PRC2 methylates histones and DNA.

    Miscellaneous databases

    NextBioi 697058.

    Gene expression databases

    Genevestigatori Q1LZ53.

    Family and domain databases

    Gene3Di 3.40.50.150. 1 hit.
    InterProi IPR025766. ADD.
    IPR018117. C5_DNA_meth_AS.
    IPR001525. C5_MeTfrase.
    IPR025811. C5_MeTrfase_3.
    IPR000313. PWWP_dom.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view ]
    Pfami PF00145. DNA_methylase. 1 hit.
    PF00855. PWWP. 1 hit.
    [Graphical view ]
    SMARTi SM00293. PWWP. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53335. SSF53335. 1 hit.
    PROSITEi PS51533. ADD. 1 hit.
    PS00094. C5_MTASE_1. 1 hit.
    PS50812. PWWP. 1 hit.
    PS51679. SAM_MT_C5. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci."
      Lees-Murdock D.J., McLoughlin G.A., McDaid J.R., Quinn L.M., O'Doherty A., Hiripi L., Hack C.J., Walsh C.P.
      Genomics 84:193-204(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).

    Entry informationi

    Entry nameiDNM3A_RAT
    AccessioniPrimary (citable) accession number: Q1LZ53
    Secondary accession number(s): Q1LZ52
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 15, 2008
    Last sequence update: May 30, 2006
    Last modified: October 1, 2014
    This is version 71 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3